Cardiovascular reflexes have a key role in regulating blood pressure. These originating in peripheral receptors, are integrated in the central nervous system, translated into differential changes in autonomic outflow to the heart and blood vessels, and further modified by local events and humoral agents at the neuro-effector junctions. The interplay between these complex events determines the amount of neurotransmitter released to govern the circulation. The studies proposed are a continuation of work aimed at increased understanding, in health and disease, of the function of these reflexes. One objective is to determine factors regulating pre- and postjunctional mechanisms in isolated blood vessels, another is to define the role of the cardiovascular reflexes in controlling the circulation during muscular exercise in conscious dogs and man. At the adrenergic neuroeffector junction experiments are planned to determine: (1) the action of metabolites produced by active cells on the nerve endings and the vascular smooth muscle; (2) the role of local cooling on the release of norepinephrine and response of blood vessels, with particular reference to cold vasodilatation and the vasospasm of Rynaud's disease (3) the contribution of adrenergic nerves to the vasoconstrictor action of cardiac glycosides; (4) the likelihood that certain plasma proteins and substances from aggregating platelets lead to vasospasm, in particular in the presence of endothelial damage and tissue ischemia and, (5) the similarities and differences between canine and human blood vessels. Studies in conscious dogs will address: (1) the pressor reflex with static exercise, and the role of arterial and cardiopulmonary reflexes. (2) The mechanisms of blood pressure regulation during rhythmic exercise when different components of the sympathetic outflow are abrogated and after acute deprivation of the carotid sinus reflex, and (3) the resetting of the latter reflex in acute and chronic hypertension, and the role of local versus central modulation. In man, the following will be observed: (1) the time-dependency in exercising muscle of blood flow response to activation of sympathetic nerves, and (2) the nature of the hemodynamic changes with static exercise due to a metabolic muscle reflex, and its modulation by other reflexes.